Implementation of any human gene therapy protocol requires experimental evidence of efficacy as defined by metabolic, pathologic, and/or clinical correction of the disease processes. In addition to efficacy, vectors used in administering genetic information must be rigorously tested for safety. Animal models play a critical role in the development of new recombinant adenoviruses, such as those currently under development for the gene therapy of cancer. Authentic animal models provide the most appropriate experimental setting in which to assess these parameters. As formalized requirements for preclinical toxicology studies are developed, it is clear that careful assessment of toxicity must be performed in at least two species of animals, one of which is a non-human primate. Further, the availability of appropriate test animals greatly simplifies the testing of gene therapies, and allows the identification of problems which would otherwise lead to patient morbidity or even mortality in the clinical setting. The University of Pennsylvania provides an outstanding environment in which to utilize animal models for the development of successful cancer gene therapy protocols. The Animal Models Core (AMC) will take a leading role in the preclinical toxicology testing of recombinant viruses. The AMC has built on the strengths of existing programs, including the University Laboratory Animal Resources and the Wistar Institute Animal Facility, to develop expertise, facilities, and resources necessary for the development of gene therapies and athe rapid application of these technologies to the treatment of cancer. The following components of the AMC will be available for testing of experimental strategies; (1) Colonies of Fischer F344 rats will be maintained for the assessment of preclinical toxicology. These mice are susceptible to adenoviral infection, and are especially useful in testing the safety in testing the safety of treatment of mesothelioma by recombinant adenoviruses. (2) To further facilitate the preclinical assessment of toxicity associated with proposed gene therapies of cancer, a specialized primate colony, which is capable of housing up to 60 primates under biohazard containment conditions in accordance with Good Laboratory Practices. Facilities and support staff will be available to appropriate participants for preclinical toxicity studies. All studies will be done with Standard Operating Procedures (SOP), to operate under Good Laboratory Practices (GLP). (3) Specialized biohazard operating room suites have been renovated at the University of Pennsylvania and the Wistar Institute for use by investigators who require animal models in which to test gene therapy strategies for the treatment of cancer, including this proposed trial for mesothelioma.